AssessmentsPlus™ Tutorial: Distribution Assessment
Simulation Assessment enables the user to gain advice on how to fit a distribution model to IV data. This is most powerful for PBPK models where the Distribution Dashboard can be used to mechanistically adjust the Kp values using the observed Vss. For the best advice on distribution, the observed clearance should be used as an input. There is also the possibility of getting descriptive advice, without fitting to observed data, via Descriptive Analysis.
In this tutorial, we will cover:
Distribution Assessment for a compartmental PK model to improve the fit
Open GPX™ and, in the Dashboard view, click on the icon next to Select to open an Existing project.
Click on Browse and navigate to the C:\Users\<user>\AppData\Local\Simulations Plus, Inc\GastroPlus\10.2\Tutorials\Distribution Assessment and select the project “Distribution Assessment” by clicking on it and clicking Open.
Navigate through the views to familiarize yourself with the assets contained in this project.
Go to the Simulations view and run the simulation called “2mg IV Bolus Comp PK” by clicking on Run Simulation. Observe the poor prediction in semi-log scale.
Click on the AssessmentsPlus™ view in the navigation pane and then click on Add. Switch the Assessment type from Compound to Simulation, enter the name “Comp PK Distribution”, and click on OK or press Enter.
Select IV for the Simulation Type and ensure that the selections for Simulation, Mode, and Scenario are as below.
Click on Assess and review the feedback.
Go to the Pharmacokinetics view and update the Vc from 20 to 9.851L in the Compartmental panel.
Go back to the AssessmentsPlus™ view and click on Assess.
Run Simulation “2mg IV Bolus Comp PK” to confirm the good prediction in semi-log scale.
Distribution Assessment for a PBPK model to improve the fit
Continue with the project created for the “Distribution Assessment for a compartmental PK model” part of this tutorial or, if that project isn’t available, follow steps 1 to 3 from above.
Run Simulation “2mg IV Bolus PBPK” and observe the poor prediction in semi-log scale.
Click on the AssessmentsPlus™ view in the navigation pane and then click Add. Switch the Assessment type from Compound to Simulation, enter the name “PBPK Distribution”, and click on OK or press Enter.
Select IV for the Simulation Type and ensure that the selections for Simulation, Mode, and Scenario are as below.
Click on Assess and review the feedback.
Go to the Pharmacokinetics view and enter the Observed Vss of 134.7L in the Distribution Dashboard and then click on Fit Kp Modifiers.
Note that Vss now matches the Observed Vss. Click on Calculate Tissue Kp.
Go back to the AssessmentsPlus™ view and click on Assess.
Run Simulation “2mg IV Bolus PBPK” to confirm the good prediction in semi-log scale.
